The clinical studies of the NIMH Collaborative Program on the psychobiology of depression involves an inter-related and coordinated group of investigations conducted on two samples drawn from five centers -- mood disordered probands and their relatives. This application seeks to continue the follow-up of the samples and to implement several new but related aims: 1.Investigation of the long-term course of illness in probands, relatives, spouses and controls; 2.determination of predictors of onset and recurrence in the same samples; 3.investigation of suicidal behavior, mortality and medical morbidity; 4.investigation of personality disorders i the samples, including validity, joint familial transmission with mood disorders, and input on clinical course of mood disorders; 5.a genetic linkage study of unipolar and bipolar families; 6.investigation of stability of diagnosis on familial modes of transmission; 7.further investigation of secular trends in the occurrence of mood disorders. These aims have important public health, clinical and research implications.